The overall objective of the UCSD/CHHC Pediatric Pharmacology Research Unit (PPRU) is to engage in studies of drugs with proven or potential activity which will lead to safe and effective therapeutic use in infants and children. This will be accomplished through careful collaborative planning and adherence to FDA guidelines so that drug files assembled during development and conduct of PPRU studies can provide sufficient data for licensing of new (or old) drugs for pediatric indications at safe, effective doses. A significant portion of this mission will be accomplished in collaboration with pharmaceutical industry so that a direct, tangible consequence of the studies performed will be to increase the number of drugs which are labeled for pediatric use and expand pediatric labeling to all pediatric populations, including newborns, so that all pediatric patients may receive intelligent and rational science-based therapy. The scope of the PPRU grant is to provide an organizational and operational infrastructure at UCSD and Children's Hospital of San Diego to implement the following specific aims: 1. To provide a locus for the conduct of studies in bioavailability, formulations, drug metabolism, pharmacokinetics, pharmacodynamics, safety and effectiveness of new drugs and drugs already in the market. 2. To gather or promote the accrual of necessary clinical data for pediatric age-specific labeling of drugs. Studies of widely used off-patent drugs and drugs used in the newborn population will be of high priority. 3. To carry out research on novel approaches and innovations in pediatric pharmacology. Specific areas of interest include, but are not limited to: a. Identification, development, validation and or extrapolation from adult studies of biomarkers of diagnosis, prognosis, efficacy, toxicity and of disease activity; b) Development and validation of non-invasive pharmacodynamic measurements; c) Development and/or adaptation of novel pharmacokinetic-pharmacodynamic modeling technology in pediatrics (e.g. mechanistic and physiologic based pharmacokinetics); d) Use of new molecular approaches; e)Applications of new drug delivery systems to pediatric therapy. 4. To implement studies of the developmental characteristics and genetic polymorphisms of drug metabolizing enzymes (DMEs), transporters, and receptors and describe phenotypic-genotypic correlations. 5. To apply pharmacogenomic and proteonomic tools in clinical studies. 6. To provide a training and educational program in clinical and developmental pharmacology.